2017 ASCO Meeting: Results from the LATITUDE Study

If you have just been diagnosed with metastatic prostate cancer and your doctor wants to start you on ADT (androgen deprivation therapy, such as Lupron), which shuts off the supply of testosterone and other male hormones, ask for abiraterone as well. It could extend your life for years.

But wait, you might be thinking (and your doctor might be telling you): abiraterone, which targets the androgen receptors, is a second-line hormonal therapy drug. It’s supposed to be given if ADT stops working. Or, if ADT stops working, you’re supposed to start chemotherapy with docetaxel.

That just changed.

Striking results from the LATITUDE clinical trial, presented in a Plenary Session of the 2017 American Society of Clinical Oncology, and to be published in the New England Journal of Medicine, show that giving abiraterone plus low-dose prednisone along with Lupron to “hormone-naïve” men (who are just starting ADT) delayed cancer progression by an average of 18 months. The study also found that adding abiraterone plus prednisone to ADT reduced the risk of death by 38%, compared with adding a placebo.

Timing Makes a Big Difference

In real estate, it’s location, location, location. With cancer drugs, scientists are learning, the key to success may be timing, timing, timing. Starting abiraterone earlier, while the cancer is more vulnerable – before it has had a chance to mutate, to develop resistance and strengthen its armor – makes a huge difference.

“This is practice-changing,” says medical oncologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation. “What’s dramatic is how much better abiraterone works when it’s given earlier. I have never seen a treatment where you could, five years later, see no progression in some men. There are some extreme responders who get a very significant remission.” It may be that abiraterone does not just stop cancer from proliferating, but it also stops, or significantly delays, cancer from mutating and becoming more resistant to treatment.

This news has the potential to affect tens of thousands of men worldwide.

“The survival outcome appears to be similar for men on ADT who take docetaxel (Taxotere) as it is for men on ADT who take abiraterone,” says medical oncologist and PCF-funded investigator Christopher Sweeney, M.B.B.S., on the faculty at the Dana-Farber Cancer Institute and Harvard Medical School, and one of the panel of experts discussing these findings at the conference.

But there are two big advantages to taking abiraterone with ADT instead of docetaxel: One is the difference in side effects. “The side effects of abiraterone are minimal, if you take your prednisone.” (Low-dose prednisone is necessary with abiraterone to help the adrenal gland make sufficient amounts of cortisol.) In contrast, there are many side effects of docetaxel; some of these include weakness, nausea, vomiting, confusion, fluid retention, anemia, and hair loss. The other is the potential, if the abiraterone-ADT combination stops working, to add docetaxel at that time.

“What LATITUDE has shown,” Sweeney continues, “is that men who develop metastases and take both abiraterone and ADT are 40 percent more likely to be alive for weddings, anniversaries, and holidays with their family five years later. This is remarkable.”

Sweeney was the lead investigator on another recent, practice-changing study presented at ASCO two years ago, called the CHAARTED trial. It found that for men who have metastatic cancer that responds to ADT (this is called hormone-sensitive prostate cancer), adding docetaxel to ADT extended the average survival from three years to nearly five. These results were huge – but Sweeney is even more excited about the results of the LATITUDE study and similar findings from the UK-led STAMPEDE trial, also presented at this year’s conference.

“The benefit we saw in CHAARTED was mainly in men who have a higher burden of disease,” notes Sweeney. “Men with a lower burden of disease lived quite a long while anyway, on average six to eight years,” with some men living much longer. “Clearly, all patients need better therapies, but men who had an average survival of three years needed help the most. We showed in that group that docetaxel extends survival – but the side effects make it difficult for some men to take it.” Men who are frail, who have other health problems, or who are elderly do not tolerate docetaxel very well.

LATITUDE began in 2012 and recruited about 1,200 patients from more than 200 medical centers worldwide until 2014; the average age of the men in the study is 68. Men were randomly assigned either to ADT and abiraterone plus prednisone, or ADT alone with a placebo.

These results are so new that it will take a while for them to ripple out from the epicenter – the ASCO meeting – throughout medical oncology. This means that many doctors don’t yet know about the benefits of starting abiraterone along with ADT.

It also means, unfortunately, that most insurance companies do not realize that this is going to be the new standard of care. They may not want to pay for abiraterone, and that’s a problem, because the drug, Zytiga, made by Janssen, is not cheap. It costs $9,000 a month; however, a generic form of abiraterone is expected to come on the market within the next two years.